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Management

Once Diagnose of HIV infection is made, base performed and recorded
 
Laboratory Investigations
  1. HIV serology; established according to HIV testing guidelines issued by NACO.
  2. Complete blood count
  3. CD4+ T lymphocyte counts (it available) or total lymphocyte count (TLC)
  4. Chest x-ray
  5. Liver Function Test especially serum alanine or aspartate aminotransferase
  6. An assessment of viral load (using HIV-1 RNA levels) is not considered essential to start therapy.
Supplementary tests indicated by history and physical examination
  1. Blood chemistry profile
  2. Hepatitis B virus (HBV) Hepatitis C virus (HCV) & serology (depending on tet availability & resources)
  3. Pregnancy test, if indicated.
  4. Urine for routine and microscopic examination  
Treatment includes
  1. Use of potent HAART and other treatment
  2. Prophylactic interventions
Table - Indications for the Initiation of Antiretroviral Therapy in Patients with HIV Infection
  1. Acute infection syndrome
  2. Chronic infection
    1. Symptomatic disease (including HIV-associated nephropathy)
    2. Asymptomatic disease
      1. CD4+ T cell count <500/La
      2. Pregnancy
  3. Postexposure prophylaxis 
 
Antiretroviral therapy
  1. Combination antiretroviral therapy or highly active antiretroviral therapy (HAART) is the correrstone of management of patients with HIV infection.
  2. Currently available drugs for treatment of HIV fall into 4 categories

Interfere with viral entry

Inhibit viral reverse transcriptase

Inhibit viral integrase enzyme

Inhibit viral protease enzyme

Interfere with binding of HIV to its receptor or coreceptor

Fusion inhibitor

Nucleoside analogue

Nucleotide analogue

Nonnucleoside RTIs

 

 

CCR5 antagonist maraviroc

Enfuvirtide

Zidovudine

Tenofovir

Nevirapine

Raltegravir

Saquinavir

Indinavir

 

 

 

Didanosine

 

Delavirdine

 

Ritonavir

 

 

Zalcitabine

 

Efavirenz

 

Nelfinavir

 

 

Stavudine

 

Etravirine

 

Amprenavir

 

 

Lamivudine

 

 

 

Fosamprenavir

 

 

Abacavir

 

 

 

Lopinavir / Ritonavir

 

 

Emtricitabine

 

 

 

Atazanavir

 

 

 

 

 

 

Tipranavir

 

 

 

 

 

 

Darunavir

 

-Initial regimen

Options to Consider

2 NRTI + PI

 

2NRTI + NNRTI

2NRTI + 2 PI

2NRTI + NNRTI

 

2NRTI + PI

2NRTI +2 PI-

3NRTI

' .,

2NRTI + NNRTI

2NRTI + PI-or 2 PI

 
Principles used for changing-regimen     
  1. A single drug should not be added or changed to a failing regimen; only if resistance testing has been done and it shows resistance to 1 drug, then it may be possible to change one drug only.
  2. Cross-resistance among NNRTls is common and therefore changing between NNRTIs should be avoided
  3. In PI therapy; nelfinavir should always be given first
  4. Cross resistance in common between ritonavir and indinavir and changing between these 2 drugs should be avoided.
Immune Reconstitution Syndrome
  1. Transient worsening of the opportunistic infection 2-3 weeks after ART initiation.
  2. The MC opportunistic infection is TB.
  3. For patients with TB, this syndrome occurs in about 30% of patients.
  4. The syndrome is characterized by fever, lymphadenopathy, worsening pulmonary lesions (at X-ray examination) and expanding central nervous system (CNS) lesions.
  5. Typically self-limiting, although may require the use of a brief course of corticosteroids to reduce inflammation for severe respiratory or CNS symptoms.
  6. ART should not be interrupted for immune reconstitution syndromes and antimicrobial therapy for the OI should be started with ART.
Prophylactic pharmacotherapy for opportunistic infections in HIV infected patients.

 
 

Group of pathogen

Pathogen

First choice

Fungal

P. Jiroveci

TMP – SMX

 

Cryptococcus neoformans

Fluconazole

 

Histoplasma capsulatum

Itraconazole

 

Coccidioides simmitis

Fluconazole

 

Penicillium marneffei

Itraconazole

Bacterial

Salmonella

Ciprofloxacin

 

Bartonella

Doxycycline / Azithromycin / Clarithromycin

 

Streptococcus pneumoniae

Pneumococcal vaccine

Mycobacterial

M. tuberculosis

INH sensitive

b. INH resistant

 

INH + pyridoxine

Rifabutin or Rifampicin

 

MAC

TMP – SMX

Protozoal

Toxoplasma gondii

TMP – SMX

Viral

Varicella zoster

Varicella zoster immune globulin

 

CMV

Ganciclovir or valganciclovir

 

HBV

Hepatitis B vaccine (3 doses)

 

HAV

Hepatitis A vaccine (2 doses)

 

Influenza

Inactivated trivalent influenza virus vaccine

 

HPV

HPV vaccine (3 doses)

 

Post Exposure Prophylaxis (PEP)
  1. The rationale behind PEP is that systemic infection does not occur immediately after an exposure, leaving a brief window of opportunity during which post exposure antiretroviral intervention may modify or prevent viral replication.
  2. PEP should be initiated preferably within 1 to 2 hours post exposure & upto 36 hours. PEP should be discouraged 72 hours after exposure. It should be administered for 28 days.-
  3. ARV regimens:
  4. Basic Regimen:- Zidovudine 300mg BD + Lamivudine 150 mg BD for 28 days
     
    Or
     
    Stavudine 30/40 BD mg + Lamivudine 150mg BD
  5. Expanded Regimen:- Above regime + Indinavir 800mg tds for 28 days.
     
    Or
     
    Above regimen + Efavirenz 600mg HS for 28 days.
  6. The health care worker should be tested for HIV as per the following schedule:
    1. Baseline HIV - At the time of exposure
    2. Repeat HIV - 6 weeks following exposure
    3. Repeat HIV - 12 weeks following exposure
    4. Repeat HIV - 6 months following exposure
  7. On all occasions the HCW should be given pre & post test counseling.
  8. During this period HCW should not
    1. Donate blood / semen / organs.
    2. Indulge in unprotected sex.
    3. Breast feed her infant
    4. Become pregnant. 
New drugs
  1. Ritonavir                  
  2. Indinavir                      
  3. Nelfinavir
  4. Atazanavir                        
  5. Tipranavir                    
  6. Darunavir
  7. Maraviroc                
  8. Entry inhibitors            
  9. Enfuvirtide 
Class specific toxicities (FAQ)
  1. NRTIs
    1. Hepatotoxicity        
    2. Lactic acidosis              
    3. Peripheral neuropathy          
    4. Pancreatitis
  2. NNRTIs
    1. Rash                        
    2. Hepatitis
  3. Pretease Inhibitors
    1. Hyperglycenia          
    2. Fat maldistripution (Lipodystrophy)              
    3. Hyperlipidemia
    4. Increased bleeding episodes in patients with hemophilia
    5. A vascular necrosis          
    6. G.I. intolerance and hepatitis  
Extra Edge: Indinavir can cause nephrolithiasis
 
Table 189-24 Indications for Changing Antiretroviral Therapy in Patients with HIV Infection
Less than a 1-log drop in plasma HIV RNA by 4 weeks following the initiation of therapy
 
A reproducible significant increase (defined as threefold or greater) from the nadir of plasma HIV RNA level not attributable to intercurrent infection, vaccination, or test methodology
 
Persistently declining CD4+ T cell numbers
 
Clinical deterioration
 
Side effects

Recent Advances

New Drugs: (Not given in Harrison 18th edition also)
  1. Maraviroc and vicriviroc: (Entry inhibitor)
    1. Acts by inhibiting virus entry via CCR5 coreceptors.
    2. It doesn’t inhibit virus taking entry with the help of CXCR4.
    3. Very potent drug and resistance is difficult to develop
    4. Side effects are hypotension due to alpha blocking action and hepatotoxicity.
  2. Tesamorelin: New drug for the treatment of lipodystrophy caused by anti HIV drugs.
  3. Raltegravir (Viral integrase inhibitor)
    1. Used in resistant HIV infection
    2. Used in combination as a part of HAART
    3. Does not cause lipodystrophy
  4. Enfuritide - Fusion inhibitor (Blocks viral entry in CD4 cells)
  5. Etravirine - NNRTI (HIV-1 inhibitor)
  6. Darunavir (HIV-1 protease inhibitor) - Refractory HIV
  7. Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate);
    1. Stribild is a once daily, fixed-dose single-tablet regimen of four drugs.
    2. Three of the four medications are active against HIV: the integrase inhibitor elvitegravir and the nucleotide/nucleoside reverse transcriptase inhibitors tenofovir NTRTI , emtricitabine NSRTI). The fourth medication is cobicistat, a drug that has no activity against HIV, but is needed to boost the blood levels and effectiveness of elvitegravir.
    3. Stribild is specifically indicated as a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naïve.
    4. Stribild is supplied as a tablet containing 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate.




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